With the widespread use of antibiotics around the world, the overuse of antibiotics is becoming more and more common. Microorganisms that develop tolerance to corresponding antibiotics have emerged, posing a new threat to human health. The emergence of drug-resistant bacteria increases the difficulty of curing infectious diseases. At present, both Gram-positive bacteria and Gram-negative bacteria have the trend of drug resistance, and the problem of drug resistance of Gram-positive bacteria is more serious. Methicillin-resistant Staphylococcus aureus is a common and highly toxic bacteria in clinic. Since its discovery, it has spread almost all over the world, and it is a very thorny problem in clinical anti-infective treatment. It is urgent to develop new antimicrobials, and many pharmaceutical companies in the world are actively looking for new drugs that can deal with multidrug-resistant bacteria. Modifying the chemical structure of existing antimicrobials under the guidance of structure-activity relationship is a common method to develop new drugs for drug-resistant bacteria.
Cassic acid is a natural anthraquinone compound (compound of formula II), which has a variety of biological and pharmacological activities and can be extracted from rhubarb. It has many effects, such as improving glucose and lipid metabolism, protecting liver, anti-fibrosis, anti-oxidation, anti-inflammation, antibacterial, anti-cancer and anti-tumor. However, its clinical application is limited to a great extent because of its poor water solubility and low bioavailability.
Crotonyl alcohol, also known as 2-butenol (compound of formula III), is an α-β unsaturated alcohol, which is obtained by condensation of acetaldehyde and then dehydration and hydrogenation of butanolaldehyde. It can also be prepared by Meerwein-Ponndorf reduction of crotonaldehyde. It is a colorless liquid with special odor. Crotonyl alcohol, as an important organic intermediate, is widely used in organic synthesis, manufacturing plasticizer, soil fumigant, herbicide, medicine, paint and so on.
In the present invention, cassic acid is modified by crotonyl alcohol to obtain a novel crotonyl alcohol cassic acid ester. Preliminary antibacterial activity experiment shows that the compound has excellent antibacterial activity and has high medical research and application value in the treatment of infectious diseases caused by multidrug resistant bacteria.